Limbic-Sensorimotor Tug of War for the Hippocampus: Dynamic Functional Connectivity as a Transdiagnostic Vulnerability Marker in Offspring of Patients With Emotion Dysregulation.

BACKGROUND

Emotion dysregulation (ED) is a key transdiagnostic symptom in several psychiatric disorders such as borderline personality disorder, bipolar disorder, and attention-deficit/hyperactivity disorder. These disorders, defined herein as ED disorders (EDDs), share similarities in symptoms, comorbidity, and heritability, emphasizing the importance of a transdiagnostic approach to identify markers of vulnerability to EDDs in high-risk populations, such as the offspring of patients with an EDD (EDDoff). The hippocampus, central to ED, exhibits alterations across EDDs.

METHODS

We used a state-of-the-art approach (micro-coactivation patterns [μCAPs]) to study the transdiagnostic dynamic functional connectivity (dFC) of hippocampal subregions from resting-state functional magnetic resonance imaging of 201 participants (74 patients with an EDD, 57 EDDoff, 70 healthy control participants). μCAPs provide a data-driven differentiation within the seed region.

RESULTS

dFC between the sensorimotor network (SMN) and the hippocampal body was lower in patients with EDDs (false discovery rate [FDR]-corrected p = .0002) and in EDDoff (pFDR = .01) than in control participants, with EDDoff displaying an intermediate pattern between patients with EDDs and control participants. dFC between the limbic network (LN) and the hippocampal head was higher in patients with EDDs than in control participants (pFDR = .01) and EDDoff (pFDR = .01). A negative correlation was found between ED and the SMN (pFDR = .01), indicating increasing ED with decreasing SMN dFC with the hippocampus.

CONCLUSIONS

Increased dFC between the hippocampal head and the LN, at the expense of the SMN, may represent a marker of disease in patients with EDDs. Lower dFC between the SMN and the hippocampal body may represent a marker of vulnerability to EDDs in EDDoff that is correlated with ED. Such a transdiagnostic construct represents a clinically relevant target for early interventions aimed at reducing vulnerability to EDDs in high-risk populations.